This proposal seeks to define factors in a PNS environment which regulate CNS neuronal regeneration. Experiments are designed to provide new information in two areas in which few data are available. The first series of experiments will test the hypothesis that components of peripheral nerve vary in their ability to support CNS neuronal regeneration. Although peripheral nerve has been shown to support regrowth of neurons in several brain regions, the relative contribution of different PNS components to nerve regeneration is not known. The regrowth of noradrenergenic neurons of the locus coeruleus in the prescence of isolated components of peripheral nerve (Schwann cells and extracellular matrix of matrix components) will be examined in tissue culture to determine the contribution by these constituents regeneration of this set of CNS neurons. The second series of experiments will test the hypothesis that different neurons have different requirements to regrow after injury. Components of peripheral nerve that support survival and outgrowth of locus coeruleus noradrenergic neurons as determined in the first set of experiments will be analyzed for support of other neurons (corticospinal and dorsal root ganglion) that extend long- projections. Length of neurite outgrowth, number of processes per neuron, and neuronal survival will be measured. Locus coeruleus, corticospinal and DRG neurons, have been selected for these studies because there is evidence to suggest that they vary in their requirements for regrowth. In vivo, locus coeruleus neurons will regenerate into a peripheral nerve environment and to some extent within the CNS environment whereas DRG neurons will regenerate within the PNS environment but not the CNS environment. Locus coeruleus neurons will be labeled by autoradiography after uptake of 3H-horepinephrine or by immunostaining for tyrosine hydroxylase. DRG neurons will be isolated by dissection. Less is known about the potential of the corticospinal neurons to regrow in either environment. However, the involvement of corticospinal neurons in locomotion makes knowledge of their potential to regrow after injury a significant concern. Lack of specific markers for corticospinal neurons has made it difficult to study their requirements for survival and regrowth. In this study these neurons will be labeled using non- toxic retrogradely transported markers.